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• W4310942327 abstract "We have been investigating the potential of cell-penetrating peptides anchored to polymeric platforms as a novel absorption enhancer which delivers biologics into systemic circulation via mucosal routes. Our previous mouse experiments demonstrated that hyaluronic acid modified with l-octaarginine, a typical cell-penetrating peptide, via a tetraglycine spacer significantly enhanced the mucosal absorption of protein drugs applied into the nasal cavities, irrespective of the molecular weights (Mw) of the drugs. The present study evaluated the performance of tetraglycine-l-octaarginine-linked hyaluronic acid applied via various mucosal routes. Somatropin (Mw: ca. 22.1 kDa) was moderately absorbed from the lung mucosa, and the mean absolute bioavailability (BA) reached 19% under enhancer-free conditions; nevertheless, its BA under intranasal administration was approximately 1% or less. Its BA significantly elevated to 46% on average through intrapulmonary coadministration with tetraglycine-l-octaarginine-linked hyaluronic acid. When the administration site was replaced with the oral cavities, an extreme reduction in somatropin absorption was observed with a mean BA of 0.056% under enhancer-free conditions. Intraoral coadministration with tetraglycine-l-octaarginine-linked hyaluronic acid resulted in a 6.3-fold elevation of somatropin absorption with statistical significance. A similar enhancement was observed under intrarectal administration with a further reduction in BA. On the other hand, the hyaluronic acid derivative did not exhibit the absorption-enhancing ability under intragastric administration, probably due to the lack of stabilization effects against enzyme-susceptible biologics. The results indicated that the intrapulmonary route was suitable for maximizing the mucosal absorption of biologics, and that there was a likelihood of the intraoral route with user convenience. When somatropin was substituted with fluorescein isothiocyanate-conjugated dextran with an average Mw range of 4–70 kDa, similar phenomena were observed under intrapulmonary and intranasal administration. BA decreased with an increase in the Mw of dextran; however, the ratio of BA under enhancer-present conditions to that under enhancer-free conditions was consistently around 3, indicating that the performance of the hyaluronic acid derivative was Mw-independent, irrespective of the administration route." @default.
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• W4310942327 date "2022-12-09" @default.
• W4310942327 modified "2023-10-17" @default.
• W4310942327 title "Performance of Cell-Penetrating Peptides Anchored to Polysaccharide Platforms Applied via Various Mucosal Routes as an Absorption Enhancer" @default.
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• W4310942327 doi "https://doi.org/10.1021/acs.molpharmaceut.2c00657" @default.
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